The critical element in the development of recombinant fusion zinc-finger proteins capable of recognizing specific 18 base-pair DNA recognition sequences will be the design of a suitable peptide linker between the modular DNA binding domains. Model hybrid recombinant fusion proteins composed of the two well-characterized zinc-finger binding proteins, Zif268 and SP1 will be constructed and assayed for their relative affinity to adjacent 9 base pair nucleotide sequences. Each zinc finger monomer consists of three modular "fingers" each of which recognizes a specific base pair triplet. Several peptide linkers will be designed and tested for their ability to allow high affinity binding of both modular zinc fingers to their respective recognition sequences. It is expected that the binding affinity of the chimeric peptide for its 18-bp target sequence will be much greater than the affinities of the individual zinc-finger domains for their individual 9-bp recognition sequences. The demonstration that these hybrid DNA-binding proteins are capable of recognizing specific, adjacent 18 base pair sequences is a critical "proof of principle" step that will permit the design of other hybrid zinc-finger proteins. These proteins may have widespread application to studies of gene regulation and as potential therapeutic agents.